Leveraging advanced sequencing technologies at UNSW’s Ramaciotti Centre for Genomics, the PreGen study is uncovering critical insights into genetic conditions in babies.
Prenatal genomic testing is giving families answers to complement ultrasounds.
Pregnancy ultrasounds can reveal physical abnormalities, which are present in 2-3% of all pregnancies. In some cases, abnormalities can cause health conditions for a baby.
If an abnormality is detected, prenatal genomic testing can be used to sequence a baby’s DNA and try to find the cause of the health conditions. The results can help families make informed decisions about treatment and management of a baby’s health.
Unfortunately, many Australians don’t have access to this life-changing resource.
But Professor Tony Roscioli, PreGen National Lead, and Group Leader in Neurogenomics at Neuroscience Research Australia (NeuRA), is trying to change that.
“The aim of the PreGen study is to kickstart prenatal genomic testing around Australia and to obtain evidence that it is useful,” says Prof. Roscioli.
In 2021, PreGen began by sequencing exomes to target disease-causing DNA mutations within genes.
“Exomes are about 1% of the total DNA in the genome,” says Prof. Roscioli. “Around 85% of disease-causing mutations will be found by just looking at 1% of the whole genome.
“After there had been an ultrasound abnormality identified in a foetus, we started exome sequencing of both parents and the baby, identifying an answer in one third of families.”
Last year, PreGen shifted to whole genome sequencing of babies and both parents, known as “trios”. The Ramaciotti Centre’s next-generation sequencing team carried out PCR-free preparation, followed by high-throughput sequencing on the NovaSeq X Plus. To date, the Centre has sequenced more than 100 genome trios.
“Since early 2023, we have worked closely with Prof. Roscioli and his team,” says Dr Helena Mangs, Deputy Director & COO of the Ramaciotti Centre. “This partnership was instrumental in validating the NovaSeq X Plus under the Centre’s NATA-accredited scope⎼ a critical step in supporting the PreGen study.”
“The Ramaciotti Centre had a genomic sequencing instrument that could sequence whole genomes at a reasonable cost,” says Prof. Roscioli.
“It’s been a fantastic collaboration. It’s worked really smoothly, and it’s shown the enormous utility of having an academic genomics centre just next door to a hospital.”
- Professor Tony Roscioli, PreGen National Lead, and Group Leader in Neurogenomics at Neuroscience Research Australia (NeuRA)
Prof. Roscioli recalls how an unexpected finding changed the lives of a family from Victoria.
“There was a heart problem seen on ultrasound, and we identified the gene responsible for that heart problem,” Prof. Roscioli says. “But in addition, we identified something completely unexpected that had not been seen on the ultrasound. It’s called an incidental finding.”
Genomic testing revealed that the baby had a rare blood disorder called congenital thrombotic thrombocytopenic purpura (cTTP). cTTP is a potentially lethal condition caused by a deficiency of the protein ADAMTS13.
“This was a gene that was related to very severe blood clotting, which you can't see on an ultrasound,” says Prof. Roscioli. “In the end, in consultation with referring doctors, the DNA changes in ADAMTS13 were reported and that saved the baby’s life. The outcome was that they could plan to deliver the baby at a tertiary hospital so they could have all the treatments available at the time of birth.”
The genomic testing allowed for a personalised treatment to be given to the baby.
“They were able to get a new targeted drug which replaced ADAMTS13, which had to be done on compassionate grounds because it’s not available generically yet,” Prof. Roscioli says.
“That little boy is now two years old and he’s completely happy and healthy, and he wouldn’t have been without this genomic testing.”
- Professor Tony Roscioli, PreGen National Lead, and Group Leader in Neurogenomics at Neuroscience Research Australia (NeuRA)
This outcome was published in the New England Journal of Medicine this year.
Prof. Roscioli hopes the PreGen study will lead to equal access to prenatal genomic testing through creation of a Medicare item number.
“We've identified that genomic testing is not equally available around the country,” Prof. Roscioli says. “Not everyone lives in a large population centre, and some people live many hours away from a hospital where they can have prenatal genomic testing.”
“A Medicare item number will also increase the availability of the test,” Prof. Roscioli says. “Some hospitals make prenatal genomic testing available while other hospitals don’t have the budget to provide it⎼ that's inequitable in a public health system.”
Although the field is still in its early stages, Prof. Roscioli is optimistic about the future of genomic sequencing for personalised medicine.
“It's taken a number of generations to do the research required to develop treatments for genetic conditions. The first step is to make a diagnosis through genomic testing. And then all the research and translation that is required enables the development and implementation of therapies.”